The aged are considered to be at a high risk from influenza infection, but the reason for this predisposition is not understood. With health care costs rising and infection figuring as the fourth leading cause of death in the elderly, the importance of preventing and reducing infections cannot be overemphasized. Recently, the Federal Government incorporated influenza vaccine into its long-term immunization program. Systemic and local lung secretory immune responses to influenza vaccine are important host defense mechanisms, but it is not known how age affects local immunity. Due to the invasive nature of the procedure required, study of local lung immunity to influenza vaccines cannot be undertaken in humans. The Principal Investigator has established Fischer-344 (F-344) inbred rat model in her laboratory to study infection and immunity in aging. Following intranasal immunization with influenza subunit vaccine, these aged rats, like humans, demonstrate markedly lower serum antibody responses compared to the young adult rats. It remains unknown whether such deficient immune responses can be reversed by administering the vaccine with an adjuvant. Muramyl dipeptide (MDP) is a suitable adjuvant in this regard since it has been shown to boost immunity to other antigens given orally. Therefore, this proposal aims to study the effects of MDP as an adjuvant in enhancing antibody responses to influenza subunit vaccine (A/Bangkok/H3N2) in F-344 rat age model. Six and 26 months old animals will be given the vaccine with and without MDP intranasally or parenterally. A booster dose of the vaccine will be given at 12 weeks. Serum and lung lavage specimens will be collected at 3, 6, 12, 13 and 16 weeks following immunization. Antibodies will be titrated by ELISA technique. Results obtained will indicate whether MDP enhances local and systemic immune responses to influenza vaccine in aged animals. A better method of immunization is the key to the success of clinical prophylactic practices. It is hoped that the results from this study would ultimately lead to a better prophylactic technique for the protection of the elderly. Improved immunization procedure could reduce the number of patients afflicted with influenza and thus have a significant impact on US hospitals during influenza seasons. This would reduce medical costs significantly. Finally, this proposed research will further assess potential value of this rat model as a tool in immunobiological studies of aging.